Deep learning for optical coherence tomography angiography: Quantifying microvascular changes in diabetic retinopathy

Optical Coherence Tomography Angiography (OCT-A) permits visualization of the changes to the retinal circulation due to diabetic retinopathy (DR), a microvascular complication of diabetes. Machine learning applications have directly benefited ophthalmology, leveraging large amounts of data to create frameworks to aid clinical decision-making. In this thesis, several techniques to quantify the retinal microvasculature are explored. First, high-quality, averaged, 6x6mm OCT-A enface images are used to produce manual segmentations for the corresponding lower-quality, single-frame images to produce more training data. Using transfer learning, the resulting convolutional neural network (CNN) segmented the superficial capillary plexus and deep vascular complex with performance exceeding inter-rater comparisons. Next, a federated learning framework was designed to allow for collaborative training by multiple participants on a de-centralized data corpus. When trained for microvasculature segmentation, the framework achieved comparable performance to a CNN trained on a fully-centralized dataset

Foveal avascular zone segmentation in optical coherence tomography angiography images using a deep learning approach

The purpose of this study was to introduce a new deep learning (DL) model for segmentation of the fovea avascular zone (FAZ) in en face optical coherence tomography angiography (OCTA) and compare the results with those of the device�s built-in software and manual measurements in healthy subjects and diabetic patients. In this retrospective study, FAZ borders were delineated in the inner retinal slab of 3 � 3 enface OCTA images of 131 eyes of 88 diabetic patients and 32 eyes of 18 healthy subjects. To train a deep convolutional neural network (CNN) model, 126 enface OCTA images (104 eyes with diabetic retinopathy and 22 normal eyes) were used as training/validation dataset. Then, the accuracy of the model was evaluated using a dataset consisting of OCTA images of 10 normal eyes and 27 eyes with diabetic retinopathy. The CNN model was based on Detectron2, an open-source modular object detection library. In addition, automated FAZ measurements were conducted using the device�s built-in commercial software, and manual FAZ delineation was performed using ImageJ software. Bland�Altman analysis was used to show 95 limit of agreement (95 LoA) between different methods. The mean dice similarity coefficient of the DL model was 0.94 ± 0.04 in the testing dataset. There was excellent agreement between automated, DL model and manual measurements of FAZ in healthy subjects (95 LoA of � 0.005 to 0.026 mm2 between automated and manual measurement and 0.000 to 0.009 mm2 between DL and manual FAZ area). In diabetic eyes, the agreement between DL and manual measurements was excellent (95 LoA of � 0.063 to 0.095), however, there was a poor agreement between the automated and manual method (95 LoA of � 0.186 to 0.331). The presence of diabetic macular edema and intraretinal cysts at the fovea were associated with erroneous FAZ measurements by the device�s built-in software. In conclusion, the DL model showed an excellent accuracy in detection of FAZ border in enfaces OCTA images of both diabetic patients and healthy subjects. The DL and manual measurements outperformed the automated measurements of the built-in software. © 2021, The Author(s)

An overview of the clinical applications of optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.Eye advance online publication, 8 September 2017; doi:10.1038/eye.2017.181

Retinal perfusion changes in radiation retinopathy-post brachytherapy for choroidal melanoma

Introduction: Radiation retinopathy (RR) is a chronic progressive vasculopathy developing secondary to the impact of ionizing radiation to the retina. RR develops post radiation therapy using radioactive plaque to treat intraocular tumors. It is not possible to predict which patients will develop RR. Changes in retinal blood oxygen saturation and blood flow could predict the future onset of RR, thereby facilitating the use of treatment such as intra-vitreal anti-vascular endothelial growth factor (VEGF). Methods: Chapter 3 and 4: Total retinal blood flow (TRBF) and retinal blood oxygen saturation (SO2) was non-invasively measured in eleven healthy human volunteers using a novel and exact provocation technique (RespirAct) that allows the precise control of the end-tidal partial pressure of oxygen (PETO2). Between-visits repeatability and within-visit variability of TRBF and SO2 measurements were assessed. Inner retinal oxygen delivery and consumption was calculated using Fick’s principle during stages of normoxia, hypoxia and hyperoxia. Chapter 5 and 6: Seventeen patients diagnosed with unilateral choroidal melanoma (CM) and eight patients who had developed unilateral ischemic RR were recruited from Ocular Oncology Clinic in the Princess Margaret Hospital, Toronto, Canada i.e. the only center all over Canada to treat CM patients with radiation therapy. The subjects underwent measurement of TRBF using a prototype methodology based upon Doppler Spectral Domain Optical Coherence Tomography (SD-OCT) and retinal vessel SO2 using a prototype Hyperspectral Retinal Camera (HRC), following pupil dilation with 1% tropicamide. In CM patients, the retinal hemodynamic parameters were studied in both eyes, before, 3months and 6months post 125Iodine plaque brachytherapy treatment. For RR patients, the measurements were taken once in both eyes after confirming the ischemic changes by wide-field fluorescein angiography. Results: Chapter 3 and 4: When the arterial PETO2 (end-tidal partial pressure of oxygen) was increased from baseline (PETO2=100mmHg) to 200 and 300mmHg, the TRBF significantly reduced (p=0.020) from 44.60 μL/min (+8.9) to 40.28 μL/min (+8.9) and 36.23 μL/min (+4.6), respectively. Retinal arteriolar SO2 (SaO2) did not show any significant change during PETO2 of 200 and 300mmHg, compared to baseline. However, retinal venular SO2 (SvO2) significantly increased (p<0.000) from 57.2% (+3.9) to 61.3% (+3.6) and 62.0% (+3.4) during PETO2 of 200 and 300mmHg, respectively, compared to baseline. Lowering the arterial PETO2, from baseline to 80, 60 and 50mmHg, TRBF significantly increased (p=0.040) from 43.17 μL/min (+12.7) to 45.19 μL/min (+5.5), 49.71 μL/min (+13.4) and 52.89 μL/min (+10.9) with simultaneous reduction in the SaO2 and SvO2 from 99.3 % (+ 5.8) and 56.3% (+ 4.2) to 95.6% (+ 5.1) and 52.5 (+ 4.1), 89.6% (+ 2.8) and 49.5% (+ 2.9), 83.3% (+ 3.9) and 45.0 % (+ 6.1), respectively (p<0.000). The group mean coefficient of repeatability (COR) for the retinal blood SaO2, SvO2 and TRBF were 18.4% (relative to a mean effect of 104.4%), 15.2% (relative to a mean effect of 60.3%), and 21.8 μL/min (relative to a mean effect of 44.72 μL/min). The overall coefficient of variability (COV) for SaO2, SvO2 and TRBF measurements were 4.7% and 6.9%, and, 15.1% respectively. The inner retinal oxygen extraction was calculated as 3.64 mLO2/min/100g tissue in humans. Chapter 5: The average TRBF in the eye with RR was significantly lower compared to the fellow eye (33.48 + 12.73 µL/min vs 50.37 + 15.26 µL/min; p = 0.013). The SaO2 and SvO2 was higher in the retinopathy eye compared to the fellow eye (101.11 + 4.26%, vs 94.45 + 5.79%; p=0.008) and (62.96 + 11.05% vs 51.24 + 6.88%, p=0.051), respectively. Chapter 6: Out of 17 CM patients recruited, 2 patient data was excluded due to poor image quality, and 3 others were lost to follow-up. During the six month follow up period, one person developed RR. The SaO2 measurement was found to be significantly increased (p=0.026) from 94.4 % (+7.9) to 98.9% (+8.8) and 100.6 % (+6.4), respectively during 3 and 6 month follow up post 125Iodine plaque brachytherapy compared to before treatment. Conclusions: Chapter 3: Our study demonstrated significant changes in retinal blood SO2 and TRBF during systemic changes in arterial PETO2. The variability in TRBF measurements may reflect the impact of subjective assessment in venous area estimation as well as Doppler signal strength differences between visits. One needs to note that, a common clinical test such as visual acuity measurement also has a reported variability of up to ±0.15 logMAR (or + 8 logMAR letters), relative to a mean effect of 0.017 logMAR (+ 4.2 letters), yet it is still being utilized as a useful clinical tool. The Doppler SD-OCT and HRC offer a quantifiable and repeatable technique of assessing retinal hemodynamics. Minimizing subjectivity in terms of blood flow analysis as well as correcting imperfections in the optics design of the HRC could possibly improve the repeatability of TRBF and retinal blood SO2, respectively. Chapter 4: Oxygen extracted from the inner retinal vessels remains unchanged during safe levels of systemic hypoxia and hyperoxia. Chapter 5: The effect of ionizing radiation has an impact on the TRBF and retinal blood SO2, clinically presenting similar to a rapidly developing diabetic retinopathy. The results show an altered retinal vascular physiology in patients with radiation related retinopathy. Chapter 6: 125Iodine brachytherapy significantly increases the retinal arteriolar blood SO2, suggesting improved retinal tissue perfusion in the treated eye. It is interesting to note that one patient developed RR in this six month period. About a 20% increase in retinal arteriolar and venular blood oxygen saturation was observed in this patient, 6 month post brachytherapy compared to pre-treatment value. In order to predict who will develop RR following brachytherapy, it is important to follow up rest of the eleven subjects to measure SO2 and TRBF during 12 and 18 month period or until they develop retinopathy. This will be a future work of interest, to recruit even large number of CM patients in a longitudinal approach. Only then a pattern or model for predicting RR in terms of SO2 or TRBF measurements could be established. The study examines the early effects of brachytherapy on retinal hemodynamics

Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally

Astigmatism and Pseudoaccommodation in Pseudophakic Eyes

noAdvanced IOLs with circumferential zones of different power provide pseudoaccommodation. We investigated the potential for power variation with meridian, namely astigmatism, to provide pseudo-accommodation. With appropriate power and axis orientations, acceptable pseudo-accommodation can be achieved